Methicillin resistant Staphylococcus aureus (MRSA) has become a serious source of life-threatening hospital infections and increasingly community acquired infections. As our current treatments for MRSA infections are losing efficacy, there is an urgent need for new antibiotics to cope with this problem. A recently discovered metabolite, bacillithiol (BSH), has been shown to be present in S. aureus and Bacillus spp., but is absent in human or other higher organisms. The specific aims of the research are to identify and characterize enzymes involved in BSH metabolism, such as bacillithiol disulfide reductase, and to elucidate S. aureus BSH dependent xenobiotic detoxification pathways. The results of these studies will elaborate the functions of BSH and will establish whether BSH metabolism is a suitable target for staphylococcal drug development. As thiols are known to be involved in the development of drug resistance, this research may provide insight into intrinsic drug resistance in S. aureus.